Schistosomiasis is one of the world's greatest health problems, affecting more than 200 million people. Invasion of skin and entrance into the bloodstream by schistosome larvae represents the initial host-parasite interaction during infection of the human host. Understanding the biochemical properties of schistosome larvae is essential not merely to obtain control of the disease they cause but to take advantage of the fundamental scientific knowledge they will provide as well. I plan to use new in vitro models of the extracellular matrix to characterize the connective tissue substrate specificity of larval proteinases. Both live cercariae and schistosomula, and isolated larval proteinases, will be tested against a variety of connective tissue macromolecules as well as models of the extracellular matrix synthesized by dermal fibroblasts, smooth muscle cells, and endothelial cells. I intend to further characterize the primary structure and active site of a proteinase I have purified from cercariae, which is released when they contact human skin lipid. I will also purify and characterize the proteolytic activity I have detected in schistosomula. Activity against IgG and complement components will be assayed to determine if proteinases may function to degrade critical host immune macromolecules as well as facilitate larval invasion. Finally, I will prepare polyclonal antisera and monoclonal antibodies to larval enzymes to both confirm their immunogenecity and also to detect sites of synthesis, storage, and release.